General anesthesia carries greater risk in horses than it does in humans or small animals. The reported incidence of anesthesia-related death is approximately 0.01% in human patients,1 0.05% in dogs,2,3 0.11% in cats,4 and 0.9% to 1.1% in horses.5–7 In horses, perioperative anesthesia-related deaths are typically the result of postanesthetic myopathyneuropathy, fracture, or cardiovascular, respiratory, or gastrointestinal complications.5–12
In horses, mortality rates associated with emergency surgical procedures performed outside of regular business hours are higher than rates associated with scheduled elective procedures.6,10,13–15 Mee et al9,10 reported mortality rates of 15.3% for horses anesthetized for emergency surgery and 0.63% for horses anesthetized and treated during regular business hours. Higher risks of death have also been found in horses ≤ 1 and ≥ 14 years of age.6 Previous studies5,11,13–22 evaluating risk factors for complications associated with general anesthesia in horses are relatively limited, and reported incidence varies widely. The most common complications in previous reports are postanesthetic myopathy and colic (or decreased fecal output), with a postoperative colic incidence rate of 45%.
General anesthesia is recommended or required for many types of ophthalmic surgery, including adnexal, corneal, and intraocular procedures, to eliminate patient movement and facilitate the use of microsurgical techniques. Although virtually all ophthalmic surgeries in horses are elective procedures, general anesthesia may also be required to maintain or restore vision, save or salvage an eye, or relieve chronic ophthalmic pain. In a study23 that compared perioperative anesthesia-related complications between horses undergoing either ophthalmic surgery or splint bone excision, the authors concluded that horses undergoing ophthalmic surgery had a significantly higher risk of having a poor recovery. In another study,24 fluconazole administration was identified as a potential risk factor for prolonged recovery in horses receiving a midazolam-ketamine combination during anesthetic induction for ophthalmic surgery. It was suggested that this was the result of inhibition of the hepatic cytochrome P450 enzyme system, which is responsible for the metabolism of various drugs, including midazolam and ketamine.24
We are not aware of previously published studies evaluating the type and incidence of complications in healthy horses administered general anesthesia for ophthalmic versus non-ophthalmic surgical procedures. As such, the objectives of the study reported here were to compare complications between healthy horses undergoing general anesthesia for ophthalmic versus non-ophthalmic procedures and identify potential risk factors for the development of complications.
Materials and Methods
Case selection criteria and medical records review
Medical records of all horses that underwent general anesthesia at the North Carolina State University Veterinary Teaching Hospital between January 2012 and December 2014 were reviewed. Horses that underwent exploratory celiotomy or that had an ASA physical status of III or higher were excluded.
Data extracted from the medical records of horses included in the study consisted of signalment; body weight; ASA physical status; medications administered before surgery, during anesthetic induction, during surgery, and during anesthetic recovery; whether fluconazole was administered prior to surgery (yes vs no); whether the procedure was performed on an emergency or planned basis and, if it was performed on an emergency basis, whether it was performed during regular hospital hours (8 am to 5 pm) or after hours (after 5 pm and before 8 am on weekdays and anytime on weekends); patient positioning; type of procedure (ophthalmic vs non-ophthalmic [orthopedic, soft tissue, or diagnostic imaging]); specific procedure performed; anesthesia, procedure, and recovery times; recovery quality (good vs poor); intraoperative and postoperative (prior to discharge) complications; and duration of postoperative hospitalization. Emergency procedures were defined as those procedures not previously scheduled or planned and those procedures performed outside of regular hospital hours. Anesthesia time was defined as the time from first administration of anesthetic induction agents until the time when administration of anesthetic maintenance agents (eg, inhalant or IV anesthetic agents) was discontinued. Procedure time was defined as the duration of the surgical or imaging procedure (ie, time from first incision to completion of surgical closure or time for image acquisition). Percentage of anesthesia time that was not procedure time was calculated as anesthesia time minus procedure time divided by anesthesia time. Recovery time was defined as the time from discontinuation of anesthetic agent administration until the time when the horse was standing. Recovery quality was subjectively graded as good or poor on the basis of observations by an experienced anesthesiologist. Complications that occurred during recovery were classified as musculoskeletal (eg, fracture or myopathy), respiratory (eg, severe epistaxis, respiratory obstruction, or prolonged apnea), or death (cardiac arrest or euthanasia). Postanesthetic complications were defined as complications that became evident after the horse was standing and were classified as musculoskeletal (eg, lameness or laminitis), respiratory (eg, tachypnea or pneumonia), gastrointestinal (mild or severe colic), ophthalmic (eg, corneal ulceration not associated with primary ocular disease), fever (rectal temperature ≥ 39.2°C [102.5°F]), other (eg, facial neuropathy or thrombophlebitis), or death (including euthanasia). Mild colic was recorded if a patient had typical clinical signs (eg, pawing, flank-watching, lying down, kicking at the abdomen, anorexia, and decreased fecal output), if colic was diagnosed on the basis of abnormal findings on transrectal palpation, or both and the patient received treatment with fluids PO or IV. The need for treatment was determined at the discretion of the attending clinician after consultation with the internal medicine service. Severe colic was recorded for patients requiring surgical intervention, IV administration of colloid fluids (eg, plasma or hetastarch), or both.
Statistical analysis
Anesthesia time, procedure time, and recovery time were compared among procedure types (diagnostic imaging, ophthalmic, orthopedic, soft tissue, and combined) by means of ANOVA. Post hoc comparisons among specific procedure types were performed with the Tukey honestly significant difference test to adjust for multiplicity. Procedure times were also compared between horses that developed complications and those that did not and between planned and emergency procedures. Relationships between procedure time and recovery time and between anesthesia time and recovery time were evaluated with linear regression analysis. An ANOVA was used to evaluate the following comparisons: procedure type, anesthesia time, recovery time, and medications administered during recovery versus recovery quality and the occurrence of postanesthetic complications; ASA physical status versus recovery time and recovery quality; and procedure type, anesthesia time, and recovery time versus the occurrence of complications during recovery. A Student t test was used to compare recovery times with and without the administration of a retrobulbar nerve block. A χ2 test was used to test for relationships between the number of medications administered during recovery and recovery quality, occurrence of postanesthetic complications and recovery quality, procedure type and occurrence of postanesthetic complications, and occurrence of complications following planned versus emergency procedures. Values of P ≤ 0.05 were considered significant. All analyses were performed with statistical software.a
Results
A total of 502 horses that underwent 556 anesthetic events were included in the study. Thirty-five breeds were represented; all horses were ASA physical status I or II. Mean ± SD age was 8.7 ± 5.5 years (median, 8.0 years; range, 0.02 to 28.0 years), and mean body weight was 501 ± 119 kg (1,103 ± 263 lb). Information on sex was available for 452 horses, of which 227 (50%) were geldings, 174 (38%) were mares, and 51 (11%) were stallions.
Of the 556 procedures, 110 (20%) were diagnostic imaging procedures, 106 (19%) were ophthalmic procedures, 246 (44%) were orthopedic procedures, 84 (15%) were soft tissue procedures, and 10 (2%) were combined procedures (soft tissue and imaging, n = 4; orthopedic and imaging, 2; ophthalmic and imaging, 2; and orthopedic and soft tissue, 1). Details of procedure types and anesthesia, procedure, recovery, and postoperative hospitalization times were summarized (Table 1). Eight technicians, 5 anesthesiology residents, and 3 board-certified veterinary anesthesiologists treated the study horses. Procedure type (diagnostic imaging, ophthalmic, orthopedic, soft tissue, or combined) was not significantly associated with age, sex, body weight, or recovery quality. However, significant differences among procedure types were found for anesthesia time, procedure time, and recovery time. Procedure, anesthesia, and recovery times were all significantly longer for ophthalmic procedures than for orthopedic and diagnostic imaging procedures. Procedure time was significantly longer for soft tissue procedures than for orthopedic procedures, and anesthesia time was significantly longer for soft tissue procedures than for orthopedic and diagnostic imaging procedures. Anesthesia and recovery times were significantly longer for combined procedures than for orthopedic and diagnostic imaging procedures. For all procedure types, there were significant (P ≤ 0.001) positive correlations between anesthesia time and recovery time and between procedure time and recovery time.
Anesthesia, procedure, recovery, and postoperative hospitalization times for 556 procedures requiring general anesthesia in horses.
| Procedure type (No.) | Anesthesia time (min) | Procedure time (min) | Recovery time (min) | Hospitalization time (d) |
|---|---|---|---|---|
| Diagnostic imaging (110) | 90.5 ± 20.3a,b,c | 65.7 ± 13.2d | 38.8 ± 14.5e,f | 3.4 ± 0.3 |
| 93 (23–125) | 70 (14–80) | 38 (10–85) | 2 (1–16) | |
| Ophthalmic (106) | 127.1 ± 53.6a,g | 95.2 ± 47.9d,h | 50.1 ± 29.6e,i | 6.3 ± 5.6 |
| 125 (20–337) | 95 (5–290) | 43.5 (6–190) | 5 (1–38) | |
| Orthopedic (246) | 91.2 ± 33.5g,j,k | 50.8 ± 6.6h,l | 37.5 ± 17.8i,m | 4.2 ± 3.9 |
| 88 (15–262) | 44.5 (5–180) | 35 (10–148) | 3 (0–28) | |
| Soft tissue (84) | 122.7 ± 55.9b,i | 86.6 ± 46.1l | 43.1 ± 8.4 | 3.3 ± 3.1 |
| 110 (30–276) | 81 (20–225) | 40 (15–100) | 2 (0–15) | |
| Combined (10) | 162.8 ± 22.4c,k | 81.5 ± 9.0 | 61.7 ± 33.3f,m | NC |
| 140 (105–181) | 72 (40–102) | 44 (25–100) | ||
| Ophthalmic and imaging (2) | NC | NC | NC | 2.0 |
| 2 (2–2) | ||||
| Orthopedic and imaging (3) | NC | NC | NC | 4.0 ± 1.4 |
| 4 (3–5) | ||||
| Soft tissue and imaging (4) | NC | NC | NC | 11.2 ± 13.9 |
| 5 (4–32) | ||||
| Orthopedic and soft tissue (1) | NC | NC | NC | 3.0 |
| NA |
Data are reported as mean ± SD, followed by median (range).
NC = Not calculated. NA = Not applicable.
Values with the same superscript letter were significantly (P ≤ 0.001) different.
Values with the same superscript letter were significantly (P = 0.013) different.
Values were significantly (P = 0.004) different.
Values were significantly (P = 0.03) different.
Values were significantly (P = 0.01) different.
Mean ± SD percentage of anesthesia time that was not procedure time was 25% ± 10%, 29% ± 13%, 46% ± 15%, and 31% ± 12% for diagnostic imaging, ophthalmic, orthopedic, and soft tissue procedures, respectively. Percentages were significantly (P ≤ 0.001) different for diagnostic imaging versus orthopedic procedures, ophthalmic versus orthopedic procedures, and soft tissue versus orthopedic procedures.
Procedure times for procedures performed on an emergency basis during regular hospital hours (n = 16; mean ± SD, 98.6 ± 31.4 minutes; median, 105 minutes; range, 50 to 150 minutes; P = 0.004) and after hours (12; mean ± SD, 124.3 ± 71.6 minutes; median, 95 minutes; range, 45 to 255 minutes; P ≤ 0.001) were significantly longer than procedure times for planned procedures (527; mean ± SD, 66.2 ± 38.6 minutes; median, 59 minutes; range, 5 to 290 minutes). Anesthesia times were also significantly longer for emergency procedures performed during regular hospital hours (mean ± SD, 137.5 ± 42.6 minutes; median, 140 minutes; range, 75 to 227 minutes; P = 0.002) and after hours (mean ± SD, 158.9 ± 85.2 minutes; median, 125.5 minutes; range, 63 to 337 minutes; P ≤ 0.001) than for planned procedures (mean ± SD, 101 ± 41 minutes; median, 95 minutes; range, 15 to 325 minutes). Recovery time following emergency procedures performed after hours (mean ± SD, 53.7 ± 38.3 minutes; median, 50 minutes; range, 20 to 148 minutes) was significantly (P = 0.033) longer than recovery time after planned procedures (mean ± SD, 40.9 ± 20.4 minutes; median, 38 minutes; range, 6 to 190 minutes).
Recovery quality was recorded for 378 of the 556 procedures. For 314 procedures, recovery quality was considered good, but for the remaining 64 procedures, recovery quality was considered poor because of the occurrence of complications. Recovery quality was not significantly associated with procedure type or with anesthesia time or procedure time. Mean ± SD recovery time was 38 ± 16 minutes (median, 35 minutes; range, 6 to 102 minutes) for good recoveries and 50 ± 28 minutes (mean, 44 minutes; range, 15 to 148 minutes) for poor recoveries, and recovery time was significantly (P ≤ 0.001) associated with recovery quality. Drugs administered during recovery included acepromazine, atipamezole, detomidine, romifidine, butorphanol, mannitol, hydrocortisone, xylazine, and yohimbine. Only yohimbine was significantly associated with a longer recovery time. A poor recovery was significantly more likely to occur when ≥ 1 medication was administered during recovery (P ≤ 0.001) or when fluconazole was administered preoperatively (P = 0.048).
Procedure type, procedure time, and anesthesia time were not significantly associated with the occurrence of complications during recovery. However, horses with a longer recovery time were significantly more likely to have respiratory (P = 0.001) or musculoskeletal (P ≤ 0.001) complications during recovery. Procedure type was not significantly associated with the occurrence of postanesthetic complications (ie, complications that were identified after the horse was standing). Longer surgery time was significantly (P = 0.020) associated with death after surgery. Longer anesthetic time was also significantly associated with death (P = 0.001) and with a combination of both postanesthetic fever and facial neuropathy (P = 0.028). Longer recovery time was significantly associated with both a combination of postanesthetic fever and other complications (P = 0.001) and with a combination of respiratory and ophthalmic complications (P = 0.007). The occurrence of postanesthetic colic was significantly associated with preoperative administration of fluconazole (P ≤ 0.001) and with administration of ≥ 10 mL of 2% lidocaine when performing a retrobulbar block (P = 0.026). Postanesthetic colic (mild or severe) developed following 86 procedures and was significantly (P ≤ 0.001) more likely to develop after planned procedures (85/527) than after emergency procedures (1/28).
Horses died or were euthanized following 10 of the 556 (1.8%) procedures. Six of those 10 horses were euthanized for reasons not directly related to anesthesia, including persistent pain or infection at the surgical site, poor long-term prognosis, poor quality of life, or a combination of these factors. The remaining 4 horses were euthanized because of catastrophic limb fracture after a diagnostic imaging procedure (n = 1) or ophthalmic procedure (1), because of prolonged recumbency with severe pyrexia after a soft tissue procedure (1), or because of a suspected adverse drug reaction with head trauma during recovery from an ophthalmic procedure (1). Complications other than euthanasia or death were recorded following 145 of the 556 (26%) procedures (Figure 1).
Complication rates (excluding euthanasia and death) following general anesthesia (GA) for 556 ophthalmic and non-ophthalmic procedures in horses.
Citation: Journal of the American Veterinary Medical Association 252, 9; 10.2460/javma.252.9.1113
The 106 ophthalmic procedures that were performed included keratectomy and grafting (n = 35); suprachoroidal cyclosporine implant placement (30); enucleation (13); penetrating keratoplasty (10); exenteration (3); keratectomy, grafting, and episcleral cyclosporine implant placement (2); phacoemulsification and intraocular lens placement (2); eyelid laceration repair (2); corneal laceration repair (1); third eyelid excision, ciliary body ablation, and suprachoroidal cyclosporine implant placement (1); third eyelid excision and cryotherapy (1); eyelid mass excision and photodynamic therapy (1); keratectomy, conjunctivectomy, and CO2 laser ablation (1); vitrectomy (1); conjunctival mass biopsy (1); eyelid laceration repair and suprachoroidal cyclosporine implant placement (1); and eyelid laceration repair, keratectomy, and grafting (1). Anesthesia time was significantly longer for keratectomy and grafting than for enucleation (Table 2). Procedure and recovery times were significantly longer for penetrating keratoplasty than for enucleation and suprachoroidal cyclosporine implant placement, and recovery time was significantly longer for penetrating keratoplasty than for keratectomy and grafting. Procedure time was significantly longer for suprachoroidal cyclosporine implant placement than for enucleation.
Surgery, anesthesia, and recovery times for 93 ophthalmic procedures requiring general anesthesia in horses.
| Procedure (No.) | Anesthesia time (min) | Procedure time (min) | Recovery time (min) |
|---|---|---|---|
| Keratectomy and grafting (35) | 146.9 ± 61.4a 131 (55–337) | 108.5 ± 54.6 100 (30–290) | 52.6 ± 23.6b 50 (17–115) |
| Penetrating keratoplasty (10) | 144.2 ± 39.0 140 (92–220) | 113.2 ± 39.5c,d 116 (55–188) | 85.0 ± 35.7b,e,f 78 (36–135) |
| Suprachoroidal cyclosporine (30) | 125.1 ± 43.5 112.5 (57–240) | 95.3 ± 1.5c,g 86 (32–195) | 41.3 ± 25.2e 35 (6–125) |
| Adnexal (5) | 85.4 ± 33.8 80 (20–112) | 57.8 ± 27.3 53 (5–85) | 48.3 ± 38.4 30 (15–72) |
| Enucleation (13) | 71.5 ± 22.9a 79.2 (41–125) | 47.4 ± 20.8d,g 51.1 (23–100) | 56.5 ± 44.6f 56.5 (22–190) |
Values with the same superscript letter were significantly (P ≤ 0.001) different.
Values with the same superscript letter were significantly (P ≤ 0.05) different.
Values were significantly (P = 0.002) different.
See Table 1 for remainder of key.
Nineteen horses were treated with fluconazole PO prior to the procedure, and all 19 underwent either penetrating keratoplasty or keratectomy and grafting. Administration of oral fluconazole was associated with significantly longer recovery times after keratectomy and grafting (P ≤ 0.001) and after both penetrating keratoplasty and keratectomy and grafting (P = 0.005). For horses that were treated with fluconazole before the procedure, recovery time when anesthesia was induced with ketamine and propofol (13 procedures) was not significantly different from recovery time when anesthesia was induced with ketamine and midazolam (6 procedures). For the 74 horses that received a retrobulbar nerve block, recovery time was significantly (P = 0.028) longer when ≥ 10 mL of 2% lidocaine was administered than when ≤ 10 mL was administered.
Discussion
Results of the present retrospective study conducted over a 3-year period (2012 through 2014) suggested that risk factors for postprocedural complications in healthy (ASA physical status I or II) horses undergoing general anesthesia for ophthalmic and non-ophthalmic procedures included preoperative oral fluconazole administration, administration of a retrobulbar nerve block with ≥ 10 mL of 2% lidocaine, long procedure and anesthetic times, a long recovery time, and administration of ≥ 1 drug during recovery. Unlike results of a previous study,24 induction of anesthesia with a midazolam-ketamine combination did not significantly increase the risk for a prolonged or poor recovery from anesthesia in the present study. Furthermore, we found that preoperative administration of fluconazole was significantly associated with an increased likelihood of postoperative signs of colic.
Fluconazole is a triazole antifungal medication that exerts its fungistatic activity by decreasing ergosterol synthesis through inhibition of the cytochrome P450 enzyme 14α-sterol demethylase. Ergosterol is an essential component of fungal cell membranes. Although fluconazole may not be highly effective against filamentous organisms, it is still used relatively frequently at our hospital as an adjunctive treatment for horses with keratomycosis because of its ability to penetrate ocular tissues at a high concentration following oral administration.25 Cytochrome P450 enzyme inhibition is relevant for other metabolic pathways in mammals, especially hepatic metabolism of certain drugs. Presumably, fluconazole similarly affects the metabolism of anesthetic drugs that use this enzyme system, including midazolam and ketamine.26–29 In contrast, propofol is rapidly metabolized in the liver by glucuronide conjugation, independent of the cytochrome P450 enzyme system.30 As such, delayed metabolism of ketamine, administered with or without midazolam, may explain the prolonged recovery time and poorer recovery quality for horses that received fluconazole in the present study. There was no significant difference in recovery times when anesthesia was induced with ketaminemidazolam versus ketamine-propofol in the present study; however, the sample sizes were small (6 and 13 horses, respectively).
A retrobulbar block is a very useful technique to provide local analgesia, relaxation of the extraocular muscles, and central positioning of the globe for horses undergoing ophthalmic surgery, eliminating the need for systemic administration of neuromuscular antagonists. Whereas an ideal volume has not been established, administration of 10 to 30 mL of 2% lidocaine has been previously recommended, depending on the size of the patient and orbit,31 with 20 mL being a typical dose used in our practice for a 500-kg (1,100-lb) horse. However, it has been our clinical experience that with accurate needle placement, a volume of 5 to 9 mL of 2% lidocaine is clinically effective. Results of the present study suggested that use of smaller volumes of lidocaine were associated with a lower risk of postoperative complications.
As for prior studies,15,21 results of the present study demonstrated the importance of minimizing procedure and anesthesia times. In our study population, longer anesthesia times for horses undergoing ophthalmic and soft tissue procedures were not associated with a higher percentage of anesthesia time that was not procedure time. Rather, the percentage of anesthesia time attributed to activities other than the procedure itself was greatest for orthopedic procedures and lowest for ophthalmic and diagnostic imaging procedures. Nonprocedural anesthesia time generally includes positioning, preparation and bandaging of the patient, and placement and set-up of surgical instruments and equipment. Because longer anesthesia times were associated with longer recovery times, a higher likelihood of postanesthetic complications, and a significantly higher risk of death, it is important to maximize efficiency in the operating room to improve patient safety.
Excluding horses euthanized because of a poor prognosis or quality of life (6/10), the mortality rate associated with anesthesia in the present study was 0.7% (4/556), which was similar to rates reported for previous studies.5–10,32 The rate of complications other than death (145/556 [26%]) was higher than rates reported previously,5,18 but this may have been a result of broader inclusion criteria in the present study. For example, facial neuropathy is a relatively common complication following general anesthesia in horses33–35 but has not been included in most previous studies evaluating postoperative complications. We speculate that this may be because this complication is considered less important, compared with other well-documented catastrophic or life-threatening complications (eg, long bone fracture), or because it resolves in most cases without treatment.
In the present study, the complication rate was comparable for patients undergoing planned procedures during regular hospital hours and for those treated after hours (after 5:00 pm and before 8:00 am on weekdays and anytime on weekends). Previous reports6,9,10,13,15 have suggested that there is increased risk of complications following procedures performed outside of regular business hours. However, the exclusion of horses with an ASA physical status higher than II and horses undergoing exploratory laparotomy from the present study may explain this discrepancy. These selection criteria excluded many horses treated on an emergency basis that likely had a high risk of postanesthetic morbidity and death. Variations in preoperative case management, duration of hospitalization preoperatively, and fasting protocol would also be expected to vary between studies.
There were several limitations of the present study, including the retrospective observational design. Inconsistencies regarding specific medications, treatment protocols, anesthetic decisions, and case management can be resolved only with a prospective controlled design. Additionally, medical records varied in the amount of data recorded, especially during the recovery and postoperative hospitalization periods (eg, number of attempts to stand during recovery or severity of postoperative signs of colic). Furthermore, the present study may have failed to investigate all relevant variables, such as other medications administered prior to surgery, that may also affect complication rates. Most patients undergoing ophthalmic procedures received 1% atropine topically prior to surgery, which may have contributed to gastrointestinal complications (eg, postanesthetic ileus).36 Methods to minimize anesthetic duration and decrease the risk of postanesthetic complications should continue to be researched. Fluconazole should be used judiciously in horses undergoing general anesthesia, and if a retrobulbar block is administered, the lowest effective volume should be used.
Acknowledgments
Presented in abstract form at the 2015 International Equine Ophthalmology Consortium Symposium, Savannah, Ga, June 2015.
The authors thank Dr. Melanie Jarrett for her assistance with data collection.
ABBREVIATIONS
| ASA | American Society of Anesthesiologists |
Footnotes
JMP Pro, version 11.0, SAS Inc, Cary, NC.
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